Hepatitis C infection in the west of Scotland : epidemiology, treatment and disease progression

Thorburn, Douglas (2001) Hepatitis C infection in the west of Scotland : epidemiology, treatment and disease progression. MD thesis, University of Glasgow.

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After the discovery of and development of diagnostic tests for hepatitis A and B it
became apparent that a parenterally transmissible agent was responsible for cases
of non-A non-B hepatitis. It was not until 1989, a further fifteen years later, that
the agent responsible for most cases, the hepatitis C virus (HCV), was identified.
This virus was initially thought to cause a mild self-limiting hepatitis. With the
introduction of serological screening tests for HCV, it was soon apparent that it
caused a chronic asymptomatic hepatitis which could be accompanied by
significant fibrosis and sometimes cirrhosis and hepatocellular carcinoma.
Epidemiological studies have since revealed that up to eighty percent of those
infected develop chronic infection and that in the developed world hepatitis C virus
infection is widespread. An estimated 0.5% of the UK population and 1.8% of the
population in the USA are infected. It is now accepted that HCV can cause an
asymptomatic indolent infection that can progress over decades with the
development of cirrhosis. Hepatitis C infection is now established as the single
most common condition referred to hepatologists and the leading indication for
hepatic transplantation in Europe and the USA.Since the discovery of the hepatitis C virus much research has focussed on the
epidemiology, natural history and treatment of the condition. The first chapter
provides an overview of HCV and places in context the research contained in this
thesis. In western countries the role of the healthcare setting in transmitting
hepatitis C virus is poorly understood. We performed a large retrospective
serological survey of hepatitis C virus infection in healthcare workers from theWest of Scotland. This revealed the overall prevalence of HCY infection in
healthcare workers to be low regardless of involvement in exposure-prone
procedures. This indicates that the risk of acquisition of hepatitis C virus infection
by healthcare workers in an area with a large HCY infected intravenous drug using
population is small and that the risk posed to patients by contact with the HCY
infected healthcare workers is also low.
Liver biopsy is the gold standard for assessing the extent of liver injury and
determining prognosis in chronic hepatitis C. Non-invasive markers of liver injury
have proved disappointing such that serial liver biopsies are required to monitor
disease progression. In this thesis the hepatocellular enzyme a-glutathione stransferase
is studied as a non-invasive marker of liver injury and as a means of
assessing response to treatment with a - interferon. Disappointingly a-glutathione
s-transferase performed poorly as a non-invasive marker of liver injury but showed
some promise as a marker of response to interferon therapy.
Three chapters of this thesis then focus on factors that may influence the natural
history of chronic hepatitis C virus infection and in particular account for the
variable rates of progression of liver fibrosis observed in chronic HCY. The role of
iron and polymorphisms in the haemochromatosis gene (HFE) were studied.
Carriage of HFE mutations was not related to the serum and liver markers of iron
accumulation or the progression of liver fibrosis. Elevated liver iron concentrations
were rarely observed, occurring in patients with more severe liver disease, and
whether this was the cause or result of hepatocellular injury was unclear. Carriage
of genetic polymorphisms in the renin-angiotensin system, which are associated
with increased systemic renin-angiotensin system activity, were studied. This novel study was designed to explore whether these polymorphisms, known to influence
the progression of renal and cardiac fibrosis in a number of cardiovascular
diseases, influenced the progression of liver fibrosis in chronic HCY. In this study
no association between these functional renin-angiotensin polymorphisms and the
progression of liver fibrosis was observed. Hepatitis G virus infection was sought
in a cohort of hepatitis C virus infected blood donors to investigate whether coinfection
with this virus influenced the severity of hepatitis C virus related liver
injury. Although hepatitis G virus co-infection was frequently observed it did not
effect the severity of liver injury assessed biochemically and histologically. The
factors that account for the variable rates of progression of chronic hepatitis C
virus infection remain to be elucidated.
Finally in this thesis the role of a - interferon therapy in the management of
asymptomatic blood donors found to have hepatitis C virus infection at blood
donation is studied. Most patients detected in this manner have only mild hepatitis
with minimal fibrosis and little data exists as to whether they are appropriate
candidates for treatment. In a randomised crossover study these patients were
observed to tolerate a. - interferon therapy and have comparable response rates to
other patient groups with chronic hepatitis C infection. These patients appear to be
suitable candidates for treatment, although more data are required to establish what
the prognosis is for these individuals if chronic HCV is left untreated.

Item Type: Thesis (MD)
Qualification Level: Doctoral
Subjects: Q Science > QR Microbiology > QR355 Virology
Colleges/Schools: College of Medical Veterinary and Life Sciences > School of Infection & Immunity > Centre for Virus Research
Supervisor's Name: Mills, Dr. Peter
Date of Award: 2001
Depositing User: Ms Dawn Pike
Unique ID: glathesis:2001-5374
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 10 Jul 2014 10:40
Last Modified: 01 Aug 2022 08:39
URI: https://theses.gla.ac.uk/id/eprint/5374

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